The major objective of this project is to investigate the interrelationships between the alterations that occur in phospholipid and energy metabolism in liver tissue from animals that are developing fatty liver due to chronic alcohol administration. We propose to determine the origin of the alteration in cellular phospholipid metabolism which gives rise to changes in the phospholipid composition of the mitochondrion. In this portion of the project we hope to determine whether alcohol administration initiates changes at the level of the endoplasmic reticulum which give rise to both fatty liver and altered phospholipids in the mitochondrion. Therefore, we plan to characterize the phospholipids in both endoplasmic reticulum and mitochondria from livers of animals on an alcohol containing diet to determine quantitatively the changes that occur in phospholipid composition of these organelles that are due to chronic alcohol administration. The transfer of phopholipids from the endoplasmic reticulum to the mitochondrion will also be measured in alcoholic rats. In addition, the contributions that the mitochondrial phospholipase A and the monoacyl phospholipid and energy metabolism, we plan to determine the effects that alcohol initiated alterations in lipid composition have on mitochondrial functional and structural integrity. To assess the alterations in phospholipid composition on the mitochondrion, we propose to measure simultaneously over a period of time during which mitochondria are allowed to deteriorate: 1. the levels of lysophosphatidylethanolamine, 2. the calcium stimulated phospholipase A activity, 3. monoacyl phospholipid reacylation, 4. ATP levels, 5. respiratory control, and 6. the ability to form a proton gradient. In addition, the ATPase activity of mitochondria from alcoholic rats will be measured under a variety of conditions utilized to alter both the energy state of the mitochondrion and the phospholipid environment of the enzyme.